Methods for Detecting Peaks in a Nucleic Acid Data Trace

Abstract

The present invention relates to methods and apparatus for detecting peaks in a sample nucleic acid data trace derived from a sample polynucleotide by (a) receiving a sequence signature of a reference polynucleotide, wherein the sequence signature comprises a profile of peak height at one or more peak position of a nucleic acid sequence data trace of one or more of reference polynucleotides; (b) receiving a sample nucleic acid sequence data trace of a sample polynucleotide corresponding to the reference polynucleotide, wherein the sample nucleic acid sequence data trace comprises a value of peak height at one or more peak position corresponding to the peak positions of the sequence signature; and (c) detecting peaks in the sample nucleic acid data trace having a peak height that correlates with the profile of peak height of the sequence signature at a corresponding peak position.

1 . A method for detecting peaks in a sample nucleic acid data trace derived from a sample polynucleotide, comprising:
 receiving a sequence signature of a reference polynucleotide, wherein the sequence signature comprises a profile of peak height at one or more peak position of a nucleic acid sequence data trace of one or more reference polynucleotides;   receiving a sample nucleic acid sequence data trace of a sample polynucleotide corresponding to the reference polynucleotide, wherein the sample nucleic acid sequence data trace comprises a value of peak height at one or more peak position corresponding to the peak positions of the sequence signature; and   detecting peaks in the sample nucleic acid data trace having a peak height that correlates with the profile of peak height of the sequence signature at a corresponding peak position.   
     
     
         2 . The method according to  claim 1 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises normalizing peak heights of the sample nucleic acid sequence data trace and detecting peaks in the sample nucleic acid sequence data trace having approximately uniform height. 
     
     
         3 . The method according to  claim 2 , wherein peak heights of the sample nucleic acid sequence data trace are normalized by the inverse of the peak height of a corresponding peak of the sequence signature. 
     
     
         4 . The method according to  claim 1 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises detecting peaks in the sample nucleic acid data trace having a peak height approximately equal to the peak height of a corresponding peak of the sequence signature. 
     
     
         5 . The method according to  claim 1 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises determining for each peak position of the reference polynucleotide a value encompassing the variance in peak height from an average peak height of a plurality of nucleic acid bases of the reference polynucleotide, and detecting peaks in the sample nucleic acid data trace at a corresponding base position having a peak height within said variance. 
     
     
         6 . The method according to  claim 1 , wherein the sequence signature of the reference polynucleotide comprises a profile of peak height of peaks of one or more nucleic acid bases as a function of peak position of a nucleic acid sequence data trace of a single reference polynucleotide. 
     
     
         7 . The method according to  claim 6 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises normalizing peak heights of the sample nucleic acid sequence data trace and detecting peaks in the sample nucleic acid sequence data trace having approximately uniform height. 
     
     
         8 . The method according to  claim 7 , wherein peak heights of the sample nucleic acid sequence data trace are normalized by the inverse of the peak height of a corresponding peak of the sequence signature. 
     
     
         9 . The method according to  claim 6 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises detecting peaks in the sample nucleic acid data trace having a peak height approximately equal to the peak height of a corresponding peak of the sequence signature. 
     
     
         10 . The method according to  claim 6 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises determining for each peak position of the reference polynucleotide a value encompassing the variance in peak height from an average peak height of a plurality of nucleic acid bases of the reference polynucleotide, and detecting peaks in the sample nucleic acid data trace at a corresponding base position having a peak height within said variance. 
     
     
         11 . An apparatus for detecting peaks in a sample nucleic acid data trace derived from a sample polynucleotide, comprising:
 (a) an input to receive information relating to a nucleic acid sequence data trace of one or more reference polynucleotides corresponding to the sample polynucleotide and to receive information relating to a nucleic acid sequence data trace of a sample polynucleotide;   (b) one or more processor operatively programmed to collectively perform the following processes:
 evaluate the nucleic acid sequence data trace of the one or more reference polynucleotides and generate a sequence signature comprising a profile of peak height, as a function of peak position, at one or more peak position of the nucleic acid sequence data trace of the one or more reference polynucleotide; 
 evaluate the sample nucleic acid sequence data trace and generate a value of peak height, as a function of peak position, at one or more peak position corresponding to a peak position of the sequence signature; 
 detect peaks in the sample nucleic acid data trace having a peak height that correlates with the profile of peak height of the sequence signature at a corresponding peak position, thereby identifying valid peaks in the nucleic acid sequence data trace of the sample polynucleotide; and 
   (c) an output to report detected peaks in the nucleic acid sequence data trace of the sample polynucleotide.   
     
     
         12 . The apparatus of  claim 11 , wherein the processor is programmed to detect peaks in the sample nucleic acid data trace by normalizing peak heights of the sample nucleic acid sequence data trace and to detect peaks in the sample nucleic acid sequence data trace having approximately uniform height. 
     
     
         13 . The apparatus of  claim 12 , wherein peak heights of the sample nucleic acid sequence data trace are normalized by the inverse of the peak height of a corresponding peak of the sequence signature. 
     
     
         14 . The apparatus of  claim 11 , wherein the processor is programmed to detect peaks in the sample nucleic acid data trace having a peak height approximately equal to the peak height of a corresponding peak of the sequence signature. 
     
     
         15 . The apparatus of  claim 11 , wherein the processor is programmed to determine, for each peak position of the reference polynucleotide, a value encompassing the variance in peak height from an average peak height of a plurality of nucleic acid bases of the reference polynucleotide, and to detect peaks in the sample nucleic acid data trace at a corresponding base position having a peak height within said variance. 
     
     
         16 . A computer system for detecting peaks in a sample nucleic acid data trace derived from a sample polynucleotide, comprising:
 (a) an input to receive information relating to a nucleic acid sequence data trace of a reference polynucleotide corresponding to the sample polynucleotide and to receive information relating to a nucleic acid sequence data trace of a sample polynucleotide;   (b) one or more processor operatively programmed to collectively perform the following processes:
 evaluate the nucleic acid sequence data trace of the reference polynucleotide and generate a sequence signature comprising a profile of peak height, as a function of peak position, at one or more peak position of the nucleic acid sequence data trace of the reference polynucleotide; 
 evaluate the sample nucleic acid sequence data trace and generate a value of peak height, as a function of peak position, at one or more peak position corresponding to a peak position of the sequence signature; 
 detect peaks in the sample nucleic acid data trace having a peak height that correlates with the profile of peak height of the sequence signature at a corresponding peak position, thereby identifying valid peaks in the nucleic acid sequence data trace of the sample polynucleotide; and 
   (c) an output to report detected peaks in the nucleic acid sequence data trace of the sample polynucleotide.   
     
     
         17 . The computer system of  claim 16 , wherein the processor is programmed to detect peaks in the sample nucleic acid data trace by normalizing peak heights of the sample nucleic acid sequence data trace and detecting peaks in the sample nucleic acid sequence data trace having approximately uniform height. 
     
     
         18 . The computer system of  claim 17 , wherein peak heights of the sample nucleic acid sequence data trace are normalized by the inverse of the peak height of a corresponding peak of the sequence signature. 
     
     
         19 . The computer system of  claim 16 , wherein the processor is programmed to detect peaks in the sample nucleic acid data trace having a peak height approximately equal to the peak height of a corresponding peak of the sequence signature. 
     
     
         20 . The computer system of  claim 16 , wherein the processor is programmed to determine, for each peak position of the reference polynucleotide, a value encompassing the variance in peak height from an average peak height of a plurality of nucleic acid bases of the reference polynucleotide, and to detect peaks in the sample nucleic acid data trace at a corresponding base position having a peak height within said variance. 
     
     
         21 . A computer readable medium having stored thereon computer executable instructions for performing a method for detecting peaks in a sample nucleic acid data trace derived from a sample polynucleotide, the method comprising:
 receiving a sequence signature of a reference polynucleotide, wherein the sequence signature comprises a profile of peak height at one or more peak position of a nucleic acid sequence data trace of one or more reference polynucleotides;   receiving a sample nucleic acid sequence data trace of a sample polynucleotide corresponding to the reference polynucleotide, wherein the sample nucleic acid sequence data trace comprises a value of peak height at one or more peak position corresponding to the peak positions of the sequence signature; and   detecting peaks in the sample nucleic acid data trace having a peak height that correlates with the profile of peak height of the sequence signature at a corresponding peak position.   
     
     
         22 . The computer readable medium according to  claim 21 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises normalizing peak heights of the sample nucleic acid sequence data trace and detecting peaks in the sample nucleic acid sequence data trace having approximately uniform height. 
     
     
         23 . The computer readable medium according to  claim 22 , wherein peak heights of the sample nucleic acid sequence data trace are normalized by the inverse of the peak height of a corresponding peak of the sequence signature. 
     
     
         24 . The computer readable medium according to  claim 21 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises detecting peaks in the sample nucleic acid data trace having a peak height approximately equal to the peak height of a corresponding peak of the sequence signature. 
     
     
         25 . The computer readable medium according to  claim 21 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises determining for each peak position of the reference polynucleotide a value encompassing the variance in peak height from an average peak height of a plurality of nucleic acid bases of the reference polynucleotide, and detecting peaks in the sample nucleic acid data trace at a corresponding base position having a peak height within said variance. 
     
     
         26 . The computer readable medium according to  claim 21 , wherein the sequence signature of the reference polynucleotide comprises a profile of peak height of peaks of one or more nucleic acid bases as a function of peak position of a nucleic acid sequence data trace of a single reference polynucleotide. 
     
     
         27 . The computer readable medium according to  claim 26 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises normalizing peak heights of the sample nucleic acid sequence data trace and detecting peaks in the sample nucleic acid sequence data trace having approximately uniform height. 
     
     
         28 . The computer readable medium according to  claim 27 , wherein peak heights of the sample nucleic acid sequence data trace are normalized by the inverse of the peak height of a corresponding peak of the sequence signature. 
     
     
         29 . The computer readable medium according to  claim 26 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises detecting peaks in the sample nucleic acid data trace having a peak height approximately equal to the peak height of a corresponding peak of the sequence signature. 
     
     
         30 . The computer readable medium according to  claim 26 , wherein the step of detecting peaks in the sample nucleic acid data trace comprises determining for each peak position of the reference polynucleotide a value encompassing the variance in peak height from an average peak height of a plurality of nucleic acid bases of the reference polynucleotide, and detecting peaks in the sample nucleic acid data trace at a corresponding base position having a peak height within said variance.